Therapy for radioisotope contamination of a large population by a dirty bomb or other event will require a cocktail of decorporation agents because of the wide variety of possible radionuclides and their chemical/biological properties. Decorporation is the only way to reduce exposure of certain incorporated radioisotopes. Fission product lanthanides and the actinides are among the most intractable of these elements to decorporate. While diethylenediaminepentacetic acid (DTPA) has been the standard therapy for actinide/lanthanide decorporation since its development and use by the U.S. Atomic Energy Commission in the 1950's, it is limited in efficacy. A new family of sequestering agents has been developed using a biomimetic design based on the similar biochemical transport properties of plutonium (IV) and iron (III). These agents are more selective and have higher affinity for plutonium (IV) and a number of other actinide metal ions. Extensive toxicity and efficacy studies using a mouse model have been published and limited tests have been done in dogs and baboons. The results established that several of the new agents are up to 30 times more effective than DTPA and, unlike DTPA, can be orally active. We have conducted additional studies with two lead compounds: 3,4,3-LI-l,2-HOPO (an octadentate ligand) and 5-LIO-Me-3,2-HOPO (a tetradentate ligand) with the intention of moving these two ligands toward clinical use by scaling up the synthesis, establishing preparation methods suitable for good manufacturing practice (GMP), carrying out limited efficacy and toxicity studies for combinations of the two chelators in a mouse model, completing toxicity studies in human cell lines, and establishing preclinical safety of the candidate ligands under good laboratory practice (GLP) guidelines. The objective of this NIH-RAID Pilot program is to enable the availability of multi-kilogram amounts of two new decorporation agents (3,4,3-LI-l,2-HOPO, an octadentate ligand, and 5-LIO-Me-3,2-HOPO, a tetradentate ligand) so that test compound availability does not become a bottleneck in studies leading to clinical availability.